1. Field of the Invention
The invention relates in general to marked prepackaged articles, and to simultaneously marking both prepackaged articles and the associated packing with substantially identical non-destructive detectable markings. The detectable markings are formed in situ on both the articles and the packaging therefor without the deposition of any ink or other external marking material, and without degrading the articles or the packaging. The simultaneous application of a pattern of marking radiation, for example, ultraviolet laser energy, to such prepackaged articles through their associated packaging causes radiation sensitive material in the article and the packaging to change to a detectable form in the pattern of the applied radiation. Thus, both can be precisionly marked with identification, security, unique, or the like information such as serial numbers, bar codes, location indicia, and the like. Such simultaneous marking can be accomplished after the articles have been fully packaged, in single or multiple units in a single package, and while the prepackaged articles remain in continuous motion. The markings on the article are preferably detectable eye through a window in the packaging. Thus, the markings on both the packaging and the article are detectable at the same time.
2. Description of the Prior Art
The pharmaceutical industry today produces billions upon billions of human consumable articles such as therapeutically effective pills, tablets, jell-caplets, and the like. These articles contain a variety of different prescription and non-prescription drugs. Due to the variety and large production quantities of these consumable articles numerous potential health problems and concerns have arisen over the possibility of confusing one product with another, or deliberate substitution, or tampering. For example, there has become an increasing need to provide direct identification on each individual consumable article, particularly therapeutically effective articles, so their origins and contents can be traced in an audit, or after the occurrence of an incident of some kind. For example, this has been found to be very valuable for the elderly where over prescription problems can result, as described in Nellhaus U.S. Pat. No. 5,845,264. Nellhaus describes the application of bar codes directly to consumable drugs by utilizing conventional high resolution printing techniques. These techniques deposit selected amounts of a marking material, such as non-toxic or inert ink, directly on the surface of the drugs. A common technique is to apply food grade ink approved by the Food and Drug Administration with an ink jet or rotary wheel printer.
Individually marking each of a plurality of individual articles has many advantages. For example, the articles can always be identified and distinguished from other articles even when removed from their containers or packaging. In addition, consumable articles, for example, can always be distinguished from other non-pharmaceutical consumable articles such as candies, and the like. With the individual marking of each consumable article, serious life threatening mistakes can be avoided. Such individual marking is also advantageous because accidental overdose situations, and the like, can be more quickly diagnosed.
Ablative laser marking of tablets had been proposed previously. Gajdos U.S. Pat. No. 4,906,813 teaches treating tablets with a gas laser beam to induce marking by ablatively burning off layers of the tablets. Riddle U.S. Pat. No. 5,294,770 teaches drilling drug release ports in pharmaceutical tablets with a laser. Undesirably, in both of these teachings, the laser energy is provided at such a high concentration as to physically burn off material from the surface of the tablet, that is, ablatively remove a portion of the material from the tablet. The removal leaves voids that can readily be seen with a 5xc3x97 or less powered microscope or lens. This ablation can cause many problems. Clear, sharp marking is difficult to achieve depending on the amount of chipping that occurs due to the ablative activity. In addition, the burning caused by the laser may chemically alter the remaining material of the tablet near the mark, which is highly undesirable in pharmaceutical applications. Thus, in order to make it feasible to mark consumable articles with a laser, a non-ablative method is needed.
Security concerns had previously prompted the proposal of numerous expedients, which purported to inhibit or eliminate tampering. Safety concerns require the processing, and, usually the packaging, of certain articles in a sterile environment, such as a clean room. Such security and safety concerns had substantially complicated the marking of articles.
Lasers are generally not presently used to mark consumable articles. Instead, the prior proposed expedients for marking pills utilized ink, frequently the ink jet process, wherein a precisely controlled amount of an edible or inert ink material was deposited directly on the surface of the pill in a predefined pattern. The prior equipment for marking pills was large, expensive, and required high maintenance. As such, the prior equipment was inherently less than perfect and introduced a significant cost increase in the production process, particularly when it was operated in a sterile environment.
Ink marking requires precise control of the objects in order to positively and accurately deposit the ink. This is troublesome since consumable articles, for example, are very small, and they must be mass produced. Individually marking each article at a cost effective rate has proven to be problematic. Production rates are limited because each article must be securely held in position relative to an ink depositing instrument. The production rate may also be undesirably reduced since each freshly marked article must not be disturbed for a particular period of time dictated by the drying requirements of the ink.
Another problem with ink marking technology is maintaining the precise location of the ink head to the article in order to apply the desired amount of ink. This is further complicated when the articles are not of a uniform size in a given batch or from batch to batch of the same or different products. A change in size or shape requires a retooling of the marking equipment. When this precise positioning is not adequately controlled, too much or too little ink may be applied, undesirably resulting in an increased scrap rate. These problems exist with ink imprinting procedures such as ink jets, stamps, rollers and the like.
Still yet another problem is that ink feed devices such as ink jet heads are inherently subject to clogging. Clogging not only increases maintenance costs, but when ink feeds clog during a marking production run, a large quantity of tablets or pills may have to be scrapped. A high scrap rate is highly undesirable.
However, one of the greatest drawbacks to utilizing ink technology to mark consumable articles is the cost associated with preparing the articles for marking. Contaminants, such as organic oils and the like, on the surface of the articles must be removed prior to marking. These contaminants undesirably reduce or eliminate legibility and durability of the ink marking. Their removal requires that special pre-treatment cleaning systems be incorporated into the process. Most pharmaceutical articles require the application of a coating of oil on their surfaces during processing, and this coating must be removed prior to marking with conventional ink techniques. Thus, in pharmaceutical applications, a special pre-treatment cleaning system is required prior to marking. The equipment used to accomplish the pre-treatment cleaning is undesirably large and expensive, and also requires high maintenance.
Given the above problems, the prior art ink based marking systems could achieve maximum production marking rates of only about 1,200 pills per minute, or 72,000 per hour.
Another drawback in utilizing ink based processes to mark consumable articles is that the ink dispenser must be close to or in direct contact with the surface of the articles to be marked. Because the prior art printing techniques required that the printing mechanism have direct access to the surfaces that were to be marked, products that had already been encapsulated in packaging materials could not be marked. It would be highly desirable to be able to mark such articles after they are encapsulated in packaging. This permits greater flexibility in production operations. Even sterile products that were packaged and then irradiated in the package for sterilization purposes, were marked before being packaged.
Another limitation of the prior art equipment is that the edible or inert marking material must satisfy Federal food and drug regulations. Thus, it would be very desirable to mark these articles without introducing any additional material.
When ultraviolet energy is absorbed by certain titanium dioxide containing materials, the titanium dioxide changes color. This phenomena has been successfully utilized to provide markings on various non-consumable objects such as wire insulation, electronic components, ceramics, glass, plastics, and the like. See, for instance, U.S. Pat. Nos. 5,501,827, 5,091,284, 5,415,939, 5,697,390, 5,111,523, 4,595,647, 4,753,863, 4,769,310, 5,030,551, 5,206,280, 5,773,494, 5,489,639, and 5,798,037, which describe the laser marking of non-consumable articles made from various materials.
Numerous materials have the capacity to change detectably and irreversibly when exposed to radiation, particularly when the radiation is in the form of a laser beam of ultraviolet radiation. See, for example, Gugger et al. U.S. Pat. No. 4,769,310 where many inorganic pigments are listed along with the color changes that occur in them as a result of exposure to radiation from an ultraviolet laser. The pigments are incorporated in the object that is to be marked. Laser energy, preferably near ultraviolet in the 0.25 to 0.38 microns range, is applied to or focused on the object, and the color change occurs in the form of the intended graphic symbols.
Articles had been conventionally marked as produced before being packaged. Where sterile packages were necessary or desired, this required that the marking facility be inside of a sterile environment, that is, inside of a clean room. This greatly complicated and increased the cost of the marking operation. The marking equipment and supplies had to be kept sterile, and the operators had to follow the procedures for maintaining a sterile environment. Those skilled in such arts recognized the need for a solution to these problems.
Those concerned with these problems recognize the need for an improved method of marking prepackaged articles.
These and other difficulties of the prior art have been overcome according to the present invention.
One object of the present invention is to provide a method of simultaneously marking discrete prepackaged articles and the associated packaging without the deposition of ink or other marking material on the articles or the packaging.
Another object of the present invention is to provide a high speed method of simultaneously marking discrete prepackaged articles and the associated packaging such that the articles can be marked on the fly, that is, they can be marked while they are in continuous motion.
Another object of the present invention is to provide a method of simultaneously marking discrete articles and their associated packaging at higher resolutions than currently possible using ink deposition techniques such as ink jet printing, and the like.
Yet another object of the present invention is to provide a method of simultaneously marking discrete prepackaged articles and the associated packaging without breaching the packaging.
It is yet another object of the present invention to provide a method of marking prepackaged discrete consumable articles and the associated packaging that does not require a pre-treatment cleaning process or post-treatment curing process.
Still yet another object of the present invention is to simultaneously mark prepackaged discrete consumable articles without etching or physically degrading the articles.
As used herein, xe2x80x9cconsumable articlesxe2x80x9d are articles intended to be consumed, orally or otherwise, by a living being, human or non-human, for therapeutic purposes, including prescription, non-prescription and food supplements. Examples of such discrete consumable articles include pills, tablets, gel caplets, dissolving tablets, lozenges, and the like.
According to the present invention individual consumable articles and the packaging associated with them are simultaneously marked by the application of irradiation energy, and without the deposition of any ink or other external marking material, and without physically degrading the articles or the packaging. As used herein, a xe2x80x9cnon-deposited markingxe2x80x9d is a marking in which no marking material, such as ink, paint or the like, is physically applied to an article or the packaging during the marking process. Physical degradation results when the amount or nature of the energy applied to an article or the packaging causes that article or the packaging to burn, melt, vaporize, or otherwise degrade leaving a crater or an otherwise visibly damaged area that is readily visible with an optical microscope having a magnification factor of 5xc3x97 or less. Such physical degradation can also include chemical degradation that alters the therapeutic nature of the product. Therapeutic degradation is not necessarily visible, however, such degradation of therapeutic effectiveness can be detected by chemical or biological analysis. Chemical degradation occurs when the degradation is sufficient to materially impair the therapeutic effectiveness or other intended usage of the article. Trace degradation that has no material effect on the intended usage is not considered to be physical degradation.
The method of the present invention comprises selecting a radiation sensitive material (dopant) that changes to a detectable color when exposed to laser or other energy, and incorporating an effective amount of that radiation sensitive material into a visible layer of the articles that are to be marked. Generally, but not necessarily, the radiation sensitive material is in the outer layer of the article. Similarly, an effective amount of the same or a different radiation sensitive material is incorporated into a window of the packaging material that is markingly associated with the article. A plurality of articles can be packaged in one package, if desired. The prepackaged articles are then preferably placed in motion and, preferably, a sensing location is established at a predetermined location or marking zone relative to a source of marking energy, such as, for example, an ultraviolet laser energy. The sensing location detects the arrival of a prepackaged article in the marking zone and triggers the firing of the marking energy, for example, a laser. Alternatively, the laser or other energy source can be moved relative to the articles and fired when it is in the proper position to mark an article, or both can be in motion when the energy source is fired. The beam of energy can be moved, without moving the source, by the use of a suitable energy beam delivery system, if desired. Also, the firing of the energy source can be synchronized to the relative movement between the articles and the energy source by some means other than a sensor that detects the arrival of an article in the marking zone. For example, the mechanism can be synchronized so that the energy source fires every time a particular station is passed by an article feed mechanism whether there is a prepackaged article in position to be marked or not, or the like. Each of the prepackaged articles is individually and instantaneously exposed to a predefined pattern of marking energy, for example, laser energy, preferably while it remains in motion. For purposes of economy a mask is very efficient in defining the pattern. Other pattern definition means can be used if desired. The marking energy is absorbed by the radiation sensitive dopant in each of the prepackaged article and the associated window of packaging according to the predefined pattern, and the radiation sensitive dopant, for example, changes color to provide the required detectable marking. In general, the detectable marking is visible to the unaided human eye. The marking may, however, be such as to be detectable by alternative means such as exposure to ultraviolet light, machine readers such as bar code readers, and the like, if desired.
Various ultraviolet generating lasers that are suitable for use in marking objects according to the present invention are well known. See, for example, Gugger et al. U.S. Pat. No. 4,769,310, where a number of lasers are listed, together with the wavelengths of the output they are capable of generating. Such lasers are well known to those skilled in the art and need not be further described here.
Preferably, the graphic information that comprises the markings according to the present invention is applied using a mask. It is possible, however, to focus a laser beam and move the beam or the object so as to form the desired graphic.
Because the laser marking occurs substantially instantaneously (typically, 10 to 20 nanoseconds), the prepackaged articles can be marked while in motion at relatively high rates of speed. For example, the prepackaged articles can be placed in motion by a conveyor system as is commonly used in many mass production facilities. However, the laser marking occurs so fast that it is possible to mark the prepackaged articles as they fall vertically under the force of gravity, thus allowing marking to be accomplished as the prepackaged articles fall from a vertical hopper, or the like. Other means of projection, such as, for example, centrifugal force, air pressure, or the like can also be used to place the prepackaged articles in motion. The rate of the prepackaged article""s movement should be synchronized with the cycle time or pulse rate of the pulsed laser or other radiation source. If very rapid pulse rates are available it may be desirable to feed the prepackaged articles at a rate that is faster than a mere gravity feed can achieve.
Significantly, no external marking material is applied to the articles or the marking window at any time. Clogging problems and drying time requirements inherent in the prior art ink marking systems are completely eliminated. Pre-treatment cleaning systems and post-treatment curing processes are no longer necessary. The problems associated with precisely positioning and holding the article relative to the ink applicators of the prior art are also eliminated.
Precise positioning and holding of the prepackaged article relative to the source of marking energy, according to the present marking process, is not required, provided the marking window and the article are both at the proper location to be marked when the marking energy system is activated. All that is required is that the area of a prepackaged article and the associated marking window that are to be marked be positioned within a relatively large focal range and roughly normal to a source of marking energy. Exposure to the source of marking energy is controlled so that no physical degradation occurs. With the essentially instantaneous marking of the articles and associated packaging, marking production rates are significantly increased, compared to prior art ink deposition marking systems.
According to one embodiment in the consumable area, 24,000 pills can be marked per minute, equating to 1,440,000 pills per hour. This is a substantial marking rate increase compared to prior art ink jet or inked rotary wheel techniques. For instance, it is twenty times faster than the conventional prior art production rate of about 1,200 pills per minute.
Because the marking results from the response by the radiation sensitive dopant in the articles and packaging to the laser or other marking energy, articles can be marked when fully encapsulated in packaging materials that are at least semi-transparent to the marking energy. Generally low concentrations of radiation sensitive dopant are provided in the packaging window, and relatively higher concentrations are found in the article. The packaging receives the highest dose of marking radiation so the minimal amount of dopant present there responds strongly. The radiation is generally somewhat attenuated when it reaches the article, but the higher concentration of radiation sensitive dopant responds more strongly than the more dilute dopant in the window of packaging. In general, the mark in the window is not as strong as in the article. The layer of the article in which the marking develops need not be the outer layer of the article so long as the layer(s) on top of the marked layer are transparent to the radiation and the marking detecting means. The marking actually occurs in situ at and below the surface of the dopant containing layer. For the marking to be visible the layer, and those above it, must be transparent enough to the visible spectrum of light that the marking is visible. The layer need not be transparent. Because the marking is near the surface a colored layer that is opaque when its entire thickness is considered can still be sufficiently translucent for the marking to be clearly visible. Consumable articles, for example, are often white in appearance because of the presence of the pigment, titanium dioxide. Where there is sufficient pigment to color the object white, the absorption of the ultraviolet energy and the resultant marking, takes place very close to the surface so that the markings are clear.
Inorganic pigments such as those listed in Gugger et al. U.S. Pat. No. 4,769,310 are suitable for use according to the present invention. Such pigments, and the changes in the detectable characteristics of such pigments under exposure to radiation are well known in the art and need not be further described or listed here. Typically, the pigments absorb radiation energy in the near ultraviolet and change color. Various organic radiation sensitive pigments such as polyethylketone and polyethylsulphone also change color when subjected to such radiation. Where the object is intended, for example, for human internal consumption, the radiation sensitive material should be one that is generally regarded as safe. A list of compositions that are generally regarded as safe is published and is well known to those skilled in the art. Titanium dioxide, for example, is generally regarded as safe. The heavy metal containing pigments are generally not on the generally regarded as safe list.
According to a preferred embodiment, an effective amount of finely divided titanium dioxide is provided in the layer of the article that is to be marked. In this instance, the surface layer contains the titanium dioxide. When exposed to a predefined pattern of laser energy in the ultraviolet range of from about 380 to 190 nanometers, precisely marked articles are produced with virtually no scrap. The markings are generally black. The markings are embedded in the layer so they are not entirely on the surface where they might be subject to erasure. They are generally visible by reason of a light colored background. Titanium dioxide is conventionally present in numerous pharmaceutical tablets and jell-caps formulations, and the like. These products can be marked with a laser according to the present invention without changing the formulation of the product so that regulatory requalification is not required. The titanium dioxide in these formulations was often intended to function as a whitening agent for the articles, and not at all for the purpose of enabling laser marking of the articles. The inclusion of a small amount of titanium dioxide dopant in an otherwise clear window of packaging material produces a slightly milky appearance, but the markings on the article are generally still visible to the unaided eye through the window. It is possible, for example, to determine whether the markings on the article are in registry with those on the window.
Generally, it is preferred the titanium dioxide be comprised of the rutile crystalline form. Also, it is preferred that the titanium dioxide be substantially white.
The titanium dioxide particles should have average diameters of less than about 10 and preferably less than 5 microns. Particle sizes of less than approximately 2 microns average are preferred. Larger particles require the use of undesirably high energy pulses. Higher and longer pulses of energy risk physical degradation and can, in extreme situations, slow the process down. The maximum duration of the pulse increases approximately with the square of the particle diameter. The following formula can be used to approximately estimate the maximum duration of the pulse that can be tolerated before physical degradation occurs.
T=D2xcfx81Cp/xcex
where T=pulse duration in nanoseconds, D=particle diameter in meters, Cp=the heat capacity of titanium dioxide (690.37 Joules per kilogram degree Kelvin), xcex=the thermal conductivity of titanium dioxide (6.55 Watts per meter degree Kelvin), and xcfx81=the particle density (4,000 kilograms per cubic meter). Read literally, this equation produces an answer in seconds. For ease of use this is converted to nanoseconds. Pulses of longer duration than those indicated by this equation will result in the application of more energy than the titanium dioxide can absorb by itself. Pulses of shorter duration should be used to avoid damaging the target article. For a particle with an average diameter of about 0.5 microns the maximum pulse duration is approximately 100 nanoseconds. As will be understood by those skilled in the art, several approximations are made in the above equation which preclude relying on it to determine anything other than the approximate order of magnitude of the maximum pulse duration times. For example, round particles are assumed. This is, of course, a very rough approximation for most particles. A constant particle diameter across all particles in the target is assumed. Again, this is only an approximation. There will always be some particle size distribution and agglomeration. This formula is useful in arriving at the order of magnitude of the maximum allowable pulse duration from which those skilled in the art can easily optimize a particular system. Effective marking can generally be achieved using significantly shorter pulses. For example, pulses of approximately 10 nanoseconds, an order of magnitude less than the maximum allowable duration, are generally effective in producing legible markings. The preferred optical pulse duration is from about 5 to 20 nanoseconds, but pulse durations of from approximately 5 to 200 nanoseconds are effective and can be employed, if desired. Some adjustment based on actual experimental results will generally be required to optimize the system. In general, the shortest pulse that is effective to produce a marking of the desired legibility should be used so as to minimize the risk of physically degrading the article. As the particle diameter increases more energy is required and the risk that energy will be dissipated by conventional heat and mass transfer processes beyond the pigment particles to the detriment of the article also increases substantially. For this reason the average diameter of the particles should be minimized.
The applied laser fluence or energy density (in Joules per square centimeter) is proportional to the diameter of the titanium dioxide particle. Without wishing to be bound by any particular theory it is believed that it should be assumed that the absorbed pulse of energy should be sufficient to heat the average pigment particle in the target article to its melting point. There should not be enough energy to change anything else in the target. Thus, where the pigment particles are the only part of the outer layers of the article that absorb ultraviolet energy, all of the energy should be absorbed by those particles. The following formula provides an approximation of the laser fluence (energy flow density) that is required.
F=2xcfx81CpD(Tmxe2x88x92Ta)/3 
Where F=the laser fluence (energy flow density) in Joules per square meter; xcfx81=the particle density (4,000 kilograms per cubic meter); Cp=the heat capacity of titanium dioxide (690.37 Joules per kilogram degree Kelvin); D=the diameter of the particle in meters; Tm=2116 degrees Kelvin, the melting point of titanium dioxide; Ta=the ambient temperature in degrees Kelvin. For ease of use the energy density is generally converted to Joules per square centimeter, and the particle diameter to microns. This equation establishes an energy threshold for a system where the pulse duration has already been established. This equation generally provides an approximation that tends to be in the middle to lower end of the acceptable range of energy flux. It provides an approximate bench-mark from which those skilled in the art can easily optimize a particular system. In general an energy flux density of from approximately 10 to 0.1, preferably, 5 to 0.1 Joules per square centimeter is effective to form a satisfactory marking. Generally an energy flux density of from approximately 1 to 0.1 is most preferred. The minimum amount of energy that is effective to produce the desired marking should generally be used. For a particle with a diameter of about 0.5 microns the starting approximation for the laser fluence is in the order of 0.17 Joules per square centimeter.
The above equations yield the following calculated values for the particle diameters that are indicated in Table I below.
The values given in Table I are order of magnitude values that provide those skilled in the art with a reliable starting point from which to optimize a particular system. Many different variables, not all of which are fully understood, enter into determining the optimum values for a particular system. For example, particle size distribution, the degree of pigment agglomeration that a particular processing system produces, and the like, all influence these values.
Energy density can generally be adjusted, optically or otherwise, through a wide range to a predetermined level as may be desired. The pulse duration, by contrast, is generally a fixed characteristic of the laser. When a laser is selected for the purposes of this invention, this inherent characteristic should be kept in mind. Most generally available ultraviolet lasers have pulse durations of less than 100 nanoseconds.
The titanium dioxide dopant should be present in the region that is to be marked in an amount ranging from approximately 0.25 to 5 weight percent, based on the weight of the layer. Preferably, the titanium dioxide is present in an amount of from about 1 to 3 weight percent in the article, and from about 0.25 to 1 in the window of packaging. The optimum density of the ultraviolet radiation on the window-article pair generally depends in part on the concentration of the titanium dioxide. Increasing the concentration of the titanium dioxide increases the risk of physical degradation. Below about 0.25 weight percent of titanium dioxide, the markings in the window tend to become faint. As the concentration of the pigment increases the clarity of the marking improves up to a point where the particles are so close together that there is a risk of degradation by reason of the concentration of absorbed energy. Where the concentration is low, on average the energy is absorbed, and the marking occurs, to a greater depth in the layer. The contrast is not as great where the concentration is so low that the marking occurs to a substantial depth in the layer. The radiation penetrates deeper into the article, and the resulting marking may not be fully detectable from the surface. The concentration of pigment or other dopant should be minimized as much as possible to avoid the necessity of using high energy densities consistent with achieving markings of acceptable contrast and crispness. Where the quality of the marking is not what is desired even at the maximum safe energy levels, the solution is to increase the concentration of the pigment rather than to degrade the window-article pair by increasing the energy level. Above a certain pigment concentration, however, the amount of energy required to generate an acceptable marking increases to an unacceptable level where degradation of the article is likely to occur. In general, pigment or other dopant concentrations of less than approximately 5 weight percent in the article are acceptable. It is assumed that the pigment is all of approximately of the same size and is equally distributed in the layer that absorbs the energy. Some processing procedures do not provide such optimum uniform distribution. Such systems should be optimized for the particular size and bulk distribution according to the teachings of the present invention.
The optimal wavelength for the ultraviolet energy is that at which the titanium dioxide absorbs energy most strongly. This is below about 400 nanometers. In general, lasers that emit ultraviolet light in the range of from about 380 to 190 nanometers are useful with those that emit energy at about 360 to 240 nanometers being preferred.
Preferably, for high volume production requirements the laser should have a pulse rate of from at least about 10 to about 1000, preferably, 20 to 400 Hertz. Pulse rate is to be distinguished from pulse duration. These are different characteristics of any given laser. Pulse rate generally defines the maximum production rate. Pulse rate indicates how many times the ultraviolet laser fires in one second, which is usually described in number of events per second (Hertz). Pulse duration indicates how long the laser is illuminated during each pulse, and is described in nanoseconds.
Other objects, advantages, and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.